2. Academic Validation
  3. A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis

A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis

  • Hepatol Commun. 2019 Feb 1;3(3):365-381. doi: 10.1002/hep4.1305.
Marlyn J Mayo 1,  Paul J Pockros 2,  David Jones 3,  Christopher L Bowlus 4,  Cynthia Levy 5,  Imran Patanwala 6,  Bruce Bacon 7,  Velimir Luketic 8 9,  Raj Vuppalanchi 10,  Sharon Medendorp 11,  Alejandro Dorenbaum 12,  Ciara Kennedy 13,  Patricia Novak 14,  Joan Gu 15,  George Apostol 16,  Gideon M Hirschfield 17
Affiliations

Affiliations

  • 1 Digestive and Liver Diseases University of Texas Southwestern Medical Center Dallas TX.
  • 2 Scripps Clinic and Scripps Translational Science Institute La Jolla CA.
  • 3 Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom.
  • 4 Division of Gastroenterology and Hepatology University of California Davis School of Medicine Sacramento CA.
  • 5 Division of Hepatology University of Miami Miller School of Medicine Miami FL.
  • 6 Royal Liverpool University Hospital and University of Liverpool Liverpool United Kingdom.
  • 7 Division of Gastroenterology and Hepatology Saint Louis University School of Medicine St. Louis MO.
  • 8 Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University School of Medicine Richmond VA.
  • 9 McGuire Research Institute, McGuire VA Medical Center Richmond VA.
  • 10 Indiana University School of Medicine Indianapolis IN.
  • 11 Premier Research Research Triangle Park NC.
  • 12 Stanford University Palo Alto CA.
  • 13 Amplyx Pharmaceuticals San Diego CA.
  • 14 Lumena Pharmaceuticals San Diego CA (one of the Shire group of companies).
  • 15 Shire Lexington MA.
  • 16 Shire Zug Switzerland.
  • 17 Toronto Centre for Liver Disease University Health Network, University of Toronto Toronto Canada.
PMID: 30859149 DOI: 10.1002/hep4.1305
Abstract

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z